ClinVar Miner

Submissions for variant NM_016341.4(PLCE1):c.4978_4981del (p.Gln1660fs)

dbSNP: rs1589475328
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Broad Center for Mendelian Genomics, Broad Institute of MIT and Harvard RCV000785963 SCV000924546 likely pathogenic Nephrotic syndrome, type 3 2023-01-25 criteria provided, single submitter curation The homozygous p.Gln1660LeufsTer9 variant in PLCE1 was identified by our study in two siblings with nephrotic syndrome (PMID: 30655312, PMID: 29127259). The p.Gln1660LeufsTer9 variant in PLCE1 has not been previously reported in individuals with nephrotic syndrome type 3. This variant has also been reported in ClinVar (Variation ID: 635085) and has been interpreted as likely pathogenic by the Broad Rare Disease Group and the Yale Center for Mendelian Genomics. This variant was absent from large population studies. This variant is predicted to cause a frameshift, which alters the protein’s amino acid sequence beginning at position 1660 and leads to a premature termination codon 9 amino acids downstream. This alteration is then predicted to lead to a truncated or absent protein. Loss of function of the PLCE1 gene is strongly associated to autosomal recessive nephrotic syndrome type 3. In summary, although additional studies are required to fully establish its clinical significance, this variant is likely pathogenic for autosomal recessive nephrotic syndrome 3. ACMG/AMP Criteria applied: PVS1_Strong, PM2_Supporting, PM3_Supporting (Richards 2015).
GeneDx RCV002508255 SCV002817985 pathogenic not provided 2022-06-28 criteria provided, single submitter clinical testing Frameshift variant predicted to result in protein truncation or nonsense mediated decay in a gene for which loss of function is a known mechanism of disease; Not observed at significant frequency in large population cohorts (gnomAD); This variant is associated with the following publications: (PMID: 25349199, 30655312)
Yale Center for Mendelian Genomics, Yale University RCV001849443 SCV002106567 pathogenic Focal segmental glomerulosclerosis 2019-01-17 no assertion criteria provided literature only
Yale Center for Mendelian Genomics, Yale University RCV001849442 SCV002107047 likely pathogenic Nephrotic syndrome 2017-11-10 no assertion criteria provided literature only

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